The broad objective of this proposal is to study the physical and chemical role of red cells influencing the events involved in hemostasis and thrombosis. We intend to investigate the interaction of both citrated and native (non-anticoagulated) blood with vascular subendothelium using an annular perfusion system. Fibrin deposition, platelet adhesion and specific measurements of thrombus height, extent and volume will be determined by a morphometric technique. The red cell number, membrane characteristics and intracellular content will be modified by in vitro techniques and the extent of modification quantified by a membrane filtration technique. The resultant effect of red cell alteration on blood interaction with subendothelium will be analyzed by classical mass transport theory to determine physical from chemical mechanisms important in the red cell which influence platelet and fibrin deposition. In addition, disease conditions in which red cell abnormalities are present, specifically polycythemia vera, sickle cell anemia and other anemias of various etiology, will be utilized to determine (1) the basic influence of red cell alterations on their physical and chemical mechanisms and (2) the extent to which such abnormalities may explain the hemostatic and/or thrombotic episodes in such disorders.